What does the chloride inside neurons have to do with seizures? · Grey Matter

Inhibition through GABA-A receptors works only while chloride inside neurons is kept low by KCC2.

What does the chloride inside neurons have to do with seizures?

Inhibition through GABA-A receptors works only while chloride inside neurons is kept low by KCC2. In the newborn brain, where the switch from NKCC1 to KCC2 is still under way, GABA inhibits weakly, which is one explanation for why neonatal seizures often resist drugs that enhance GABA-A receptors. In adult epileptic tissue and after intense activity, KCC2 can fall or chloride can build up, so GABA loses part of its brake when it is needed most. Restoring the chloride gradient is therefore studied as a treatment strategy, though blocking NKCC1 with bumetanide has not shown clear benefit in newborns.